Predicting Human Splicing Branchpoints By Combining Sequence-Derived Features And Multi-Label Learning Methods, Wen Zhang, Xiaopeng Zhu, Yu Fu, Junko Tsuji, Zhiping Weng
Program in Bioinformatics and Integrative Biology Publications and Presentations
BACKGROUND: Alternative splicing is the critical process in a single gene coding, which removes introns and joins exons, and splicing branchpoints are indicators for the alternative splicing. Wet experiments have identified a great number of human splicing branchpoints, but many branchpoints are still unknown. In order to guide wet experiments, we develop computational methods to predict human splicing branchpoints.
RESULTS: Considering the fact that an intron may have multiple branchpoints, we transform the branchpoint prediction as the multi-label learning problem, and attempt to predict branchpoint sites from intron sequences. First, we investigate a variety of intron sequence-derived features, such as ...
Alterations In Mrna 3' Utr Isoform Abundance Accompany Gene Expression Changes In Human Huntington's Disease Brains, 2017 University of Massachusetts Medical School
Alterations In Mrna 3' Utr Isoform Abundance Accompany Gene Expression Changes In Human Huntington's Disease Brains, Lindsay S. Romo, Ami Ashar-Patel, Edith L. Pfister, Neil Aronin
Open Access Articles
The huntingtin gene has two mRNA isoforms that differ in their 3' UTR length. The relationship of these isoforms with Huntington's disease is not established. We provide evidence that the abundance of huntingtin 3' UTR isoforms differs between patient and control neural stem cells, fibroblasts, motor cortex, and cerebellum. Huntingtin 3' UTR isoforms, including a mid-3' UTR isoform, have different localizations, half-lives, polyA tail lengths, microRNA sites, and RNA-binding protein sites. Isoform shifts in Huntington's disease motor cortex are not limited to huntingtin; 11% of alternatively polyadenylated genes change the abundance of their 3' UTR isoforms. Altered expression ...
A Role For Tau Protein In Maintaining Ribosomal Dna Stability And Cytidine Deaminase-Deficient Cell Survival, 2017 PSL Research University
A Role For Tau Protein In Maintaining Ribosomal Dna Stability And Cytidine Deaminase-Deficient Cell Survival, Elias Bou Samra, Geraldine Buhagiar-Labarchede, Christelle Machon, Jerome Guitton, Rosine Onclercq-Delic, Michael R. Green, Olivier Alibert, Claude Gazin, Xavier Veaute, Mounira Amor-Gueret
Open Access Articles
Cells from Bloom's syndrome patients display genome instability due to a defective BLM and the downregulation of cytidine deaminase. Here, we use a genome-wide RNAi-synthetic lethal screen and transcriptomic profiling to identify genes enabling BLM-deficient and/or cytidine deaminase-deficient cells to tolerate constitutive DNA damage and replication stress. We found a synthetic lethal interaction between cytidine deaminase and microtubule-associated protein Tau deficiencies. Tau is overexpressed in cytidine deaminase-deficient cells, and its depletion worsens genome instability, compromising cell survival. Tau is recruited, along with upstream-binding factor, to ribosomal DNA loci. Tau downregulation decreases upstream binding factor recruitment, ribosomal RNA synthesis ...
Flt1 And Transcriptome-Wide Polyadenylation Site (Pas) Analysis In Preeclampsia, 2017 University of Massachusetts Medical School
Flt1 And Transcriptome-Wide Polyadenylation Site (Pas) Analysis In Preeclampsia, Ami Ashar-Patel, Yasin Kaymaz, Augustine Rajakumar, Jeffrey A. Bailey, S. Ananth Karumanchi, Melissa J. Moore
Open Access Articles
Maternal symptoms of preeclampsia (PE) are primarily driven by excess anti-angiogenic factors originating from the placenta. Chief among these are soluble Flt1 proteins (sFlt1s) produced from alternatively polyadenylated mRNA isoforms. Here we used polyadenylation site sequencing (PAS-Seq) of RNA from normal and PE human placentae to interrogate transcriptome-wide gene expression and alternative polyadenylation signatures associated with early-onset PE (EO-PE; symptom onset < 34 weeks) and late-onset PE (LO-PE; symptom onset > 34 weeks) cohorts. While we observed no general shift in alternative polyadenylation associated with PE, the EO-PE and LO-PE cohorts do exhibit gene expression profiles distinct from both each other and from normal placentae. The only two genes upregulated ...
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, 2017 University of Nebraska Medical Center
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch
Theses & Dissertations
DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4—; 40% penetrance (17/42)). In contrast, mono-allelic inactivation of Dnmt3a results in the presentation of CLL ...
Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer, 2017 George Washington University
Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer, Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath
Open Access Articles
Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent ...
Replication Fork Slowing And Stalling Are Distinct, Checkpoint-Independent Consequences Of Replicating Damaged Dna, 2017 University of Massachusetts Medical School
Replication Fork Slowing And Stalling Are Distinct, Checkpoint-Independent Consequences Of Replicating Damaged Dna, Divya Ramalingam Iyer, Nicholas R. Rhind
Open Access Articles
In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions ...
Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, 2017 University of Pennsylvania
Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, Xiang Yu, James W. Davenport, Karen A. Urtishak, Marie L. Carillo, Sager J. Gosai, Christos P. Kolaris, Jo Ann W. Byl, Eric F. Rappaport, Neil Osheroff, Brian D. Gregory, Carolyn A. Felix
Departmental Papers (Biology)
Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We ...
Anxiety Associated Increased Cpg Methylation In The Promoter Of Asb1: A Translational Approach Evidenced By Epidemiological And Clinical Studies And A Murine Model, Rebecca T. Emeny, Jens Baumert, Anthony S. Zannas, Sonja Kunze, Simone Wahl, Stella Iurato
Open Dartmouth: Faculty Open Access Articles
Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n= 1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders ...
A Review Of Ankylosing Spondylitis, 2017 Department of Biology and Chemistry
A Review Of Ankylosing Spondylitis, Hannah L. Owen
Senior Honors Theses
Ankylosing spondylitis (AS) is a systemic autoimmune disorder that induces ankylosis of the spine (fusion of the vertebrae at their various joints) and inflammatory arthritis of peripheral joints among other symptoms. Overexpression of cytokines, the presence of genetic mutations not exclusive to the human leucocyte antigen (HLA)-B27 region, and environmental factors all have large roles in the progressive development of AS. Although a definitive pathology continues to be sought after, researchers believe the adaptive immune system in AS patients attacks fibrocartilaginous entheses (supportive connective tissue between bone and attached structures like tendon, ligament, and fascia).
AS markedly reduces proper ...
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, 2017 Western University
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince
Western Research Forum
Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at ...
Is It Time To Start Using Mitochondrial Dna Copy Number As An Indicator Of Health And Diseases?, 2017 Touro College of Osteopathic Medicine (Middletown)
Is It Time To Start Using Mitochondrial Dna Copy Number As An Indicator Of Health And Diseases?, Vasudeva G. Kamath
Touro College of Osteopathic Medicine (Middletown) Publications and Research
The author discusses whether the medical community should seriously investigate the numerical relation of mitochondrial DNA copy number as a health indicator.
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, 2017 University of Colorado Boulder
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, Hannah Young
Undergraduate Honors Theses
One of the hallmarks of schizophrenia is the presence of psychosis. However, subthreshold psychotic symptoms characterized by attenuated delusions and hallucinations also occur in healthy individuals from the general population. A body of evidence suggests that this phenomenon represents a continuum of schizophrenia, with severe and attenuated symptoms sharing a common genetic etiology. Hallucinations are one subthreshold psychotic symptom in which a clear continuum has been observed. The aim of this study is to assess if subthreshold hallucinatory experiences and schizophrenia share genetic liability.
3,028 participants were administered the Launay-Slade Hallucination Scale (LSHS), which measures a predisposition ...
The Autocrine Role Of Proteoglycan-4 (Prg4) In Modulating Osteoarthritic Synoviocyte Proliferation And Expression Of Matrix Degrading Enzymes, Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, Khaled A. Elsaid
Pharmacy Faculty Articles and Research
Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)- stimulated conditions.
Methods: Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear translocation ...
Exercise Recommendations For Active Adults At Risk For Sudden Cardiac Death: “Can I Continue To Exercise?”, 2017 University of South Carolina
Exercise Recommendations For Active Adults At Risk For Sudden Cardiac Death: “Can I Continue To Exercise?”, Kacie Lynn Baker
Theses and Dissertations
Sudden arrhythmic death syndrome (SADS) is due to genetic conditions associated with cardiac ion channelopathies and cardiomyopathies. Many of these conditions have exercise guidelines regarding eligibility and disqualification recommendations for competitive athletes through the American Heart Association and the American College for Cardiology. This study investigates how medical professionals communicate these exercise recommendations to patients, and in turn, how well patients understand these recommendations. The study also explores motivations for either continuing or discontinuing an exercise practice after a diagnosis. A questionnaire was distributed through cardiac disease-focused support groups and organizations. Data from 67 individuals with a SADS condition were ...
The Perceived Utility Of Personalized Genomic Medicine In Individuals With A Family History Of Heart Disease: A Pilot Study, 2017 University of South Carolina
The Perceived Utility Of Personalized Genomic Medicine In Individuals With A Family History Of Heart Disease: A Pilot Study, Dana Margaret Mittag
Theses and Dissertations
According to the World Health Organization (2005), cardiovascular disease (CVD) is the number one cause of death in most countries. Assessing a patient’s risk for heart disease may include incorporating factors such as their gender, age, weight, tobacco history, cholesterol, blood pressure, family history, and more recently, genetics. Genome-wide association studies (GWAS) have made it possible to identify risk loci for many of the common, complex disorders, including coronary artery disease (CAD). As the medical genetics community undergoes a shift from a genetics focus to a genomics oriented focus, genomic medicine is becoming more accessible. Research has begun to ...
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, 2016 University of New England
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, Meghan May
Biomedical Sciences Faculty Presentations
Dr. Meghan May gives an overview presentation of her research on evolution of virulence and pathogen prediction. The focus of the presentation is a group of organisms called mycoplasmas, and covered subjects include: Mycoplasma synoviae, Mycoplasma gallisepticum, genomic context, predictive modeling, sequence evolution, and genome reduction.
Regulation Of Polycystin-1 Function By Calmodulin Binding, 2016 University of California, Santa Barbara
Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs
Pharmacy Faculty Articles and Research
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal ...
Investigation Of Genetic Markers In Sub-Elite Australia Rules Football Players, 2016 The University of Notre Dame Australia
Investigation Of Genetic Markers In Sub-Elite Australia Rules Football Players, Ysabel Jacob, Ashley Cripps, Tess Evans, Paola Chivers, Christopher Joyce, Ryan Anderton
Law And The Sciences Of The Brain/Mind, 2016 University of Pennsylvania Law School
Law And The Sciences Of The Brain/Mind, Stephen J. Morse
This chapter is a submission to the Oxford Handbook of Law and the Regulation of Technology edited by Roger Brownsword. It considers whether the new sciences of the brain/mind, especially neuroscience and behavioral genetics, are likely to transform the law’s traditional concepts of the person, agency and responsibility. The chapter begins with a brief speculation about why so many people think these sciences will transform the law. After reviewing the law’s concepts, misguided challenges to them, and the achievements of the new sciences, the chapter confronts the claim that these sciences prove that we are really not ...